Breast Atypical Ductal HyperplasiaPhase 3NCT01905046
Metformin Hydrochloride in Preventing Breast Cancer in Patients With Atypical Hyperplasia or In Situ Breast Cancer
A Phase 3 study testing metformin hydrochloride in people with Breast Atypical Ductal Hyperplasia and Breast Ductal Carcinoma In Situ, run by Alliance for Clinical Trials in Oncology at 27 sites in United States.
Trial summary
This phase III trial studies how well metformin hydrochloride works compared to placebo in preventing breast cancer in patients with atypical hyperplasia or in situ breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of metformin hydrochloride may prevent breast cancer. Read more about this study
- Who is it for?
- Ages 25 to 55 years, women only
- Conditions the study is for
- Breast Atypical Ductal Hyperplasia, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ
- What is being tested?
- metformin hydrochloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 27 sitesUnited States
- Study dates
- 23 Nov 2015to Nov 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
None listed.
Who cannot join
- Other active malignancy =< 5 years prior to pre-registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment, i.e., other hormonal therapy, for their cancer
- Body mass index (BMI) < 25
- Receiving Warfarin
- Bilateral breast implants or autologous breast flap reconstruction
- Active diagnosis of alcoholism
- Contraindication to metformin prevention such as acute hypersensitivity or allergic reaction to metformin
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- Currently receiving tamoxifen or raloxifene
- Administration of any investigational agent =< 30 days prior to pre-registration
- Previous radiation to both breasts
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving pyrimethamine, cimetidine, rifampin or cephalexin
- Women who have a core biopsy or excisional biopsy containing invasive cancer
- Women who have taken metformin within the past 90 days
- Patients with hemoglobin a1c > 6.3 or who are being actively treated for diabetes
Trial locations and contacts
27 sites in 1 country.
27 sites in 1 country
United States27 sites
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Roswell Park Cancer Institute
Buffalo, New York, 14263
The Christ Hospital
Cincinnati, Ohio, 45219
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640
Greenville Health System Cancer Institute-Andrews
Greenville, South Carolina, 29601
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Prisma Health Greenville Memorial Hospital
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650
M D Anderson Cancer Center
Houston, Texas, 77030
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Doctor's Hospital of Laredo
Laredo, Texas, 78041
Los Angeles County-USC Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
The Community Hospital
Munster, Indiana, 46321
Mount Sinai Hospital
New York, New York, 10029
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, 29672
City of Hope South Pasadena
South Pasadena, California, 91030
Cotton O'Neil Cancer Center / Stormont Vail Health
Topeka, Kansas, 66606
About this study
Official title: Testing for Atypia in Random Periareolar Fine Needle Aspiration (RPFNA) Cytology After 12 Months Metformin (1, 1-Dimethylbiguanide Hydrochloride) Chemoprevention Versus Placebo Control in Premenopausal Women
This phase III trial studies how well metformin hydrochloride works compared to placebo in preventing breast cancer in patients with atypical hyperplasia or in situ breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of metformin hydrochloride may prevent breast cancer.
Read the detailed description
- Test for the presence or absence of cytological atypia (as measured by a Masood Cytology Index Score of 14-17) in unilateral or bilateral random periareolar fine needle aspiration (RPFNA) aspirates after 12 and 24 months (24 month is optional for placebo-only group for patients who remain on placebo arm and will not receive metformin [metformin hydrochloride]) for women receiving metformin versus placebo control. The presence of cytological atypia means any atypia in any RPFNA specimen.
SECONDARY OBJECTIVES:
- Use the Masood Cytology Index Score to test for the presence of cytological atypia or disappearance of cytological atypia in RPFNA aspirates after 12 months for both arms, and 24 months (24 month is optional for placebo-only group for patients who remain on placebo arm and will not receive metformin, and mandatory for crossover patients) for women receiving metformin 850 mg orally (PO) twice daily (BID) (metformin group).
II. Compare Masood Cytology Score values at 0 and 12 months in right and left breasts (if both breasts were aspirated) from the same individual in the metformin and placebo group.
III. Test the reproducibility of reverse phase protein microarray (RPPM) in duplicate RPPM determinations from individual RPFNA specimens.
IV. Correlate baseline RPPM values with presence of atypia (as measured by Masood Cytology Index Score) at month 12 and month 24 (month 24 optional for placebo-only group; for patients who remain on placebo arm and will not receive metformin) RPFNA.
TERTIARY OBJECTIVES:
- Test whether metformin alters RPFNA or blood biomarkers associated with breast cancer risk.
II. Test whether metformin alters markers associated with obesity and insulin resistance.
III. Test other exploratory measures in RPFNA and serum including metformin levels and estrogen/progesterone.
IV. Banking: As part of ongoing research for Alliance Cancer Control studies, banking residual blood and RPFNA products for future studies.
- Conditions
- Breast Atypical Ductal Hyperplasia, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ
- Being tested
- metformin hydrochloride, placebo
- Medical subject headings
- Carcinoma, Intraductal, Noninfiltrating, Breast Carcinoma In Situ
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metformin hydrochlorideDrug
Also called 1,1 - dimethylbiguanide hydrochloride, 657-24-9, N, N - dimethylimidodicarbonimidic diamide monohydrochloride
given PO
placeboOther
Also called PLCB
given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I: metformin hydrochloride | Experimental | Patients receive metformin hydrochloride PO QD or BID for 24 months. Patients will continue metformin 850 mg PO BID for months 13-24. Patients will undergo RPFNA at 24 months. Follow up visits will be performed at 36 and 48 months after the start of treatment. Receives: Drug: metformin hydrochloride |
| Arm II: placebo | Placebo comparator | Patients receive placebo PO QD or BID for 12 months. Patients may crossover to Arm I for months 13-24. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Test for the Presence or Absence of Cytological Atypia in Unilateral or Bilateral RPFNA Aspirates After 12 Months.
Presence of atypia at 12 months is determined through the average of Masood scores across all evaluable breasts for a patient. If the average score is at least 13.5, then patient will be labeled as having atypia. The primary aim of this study is to compare the presence of atypia at month 12 between two arms using the chi-square test in univariable analysis and regressed on group indicator, age, race, stratification factors, and baseline Masood score using logistic regression in multivariable analysis.
Measured: 12 months
Secondary outcomes (4)
Test for the Masood Score and the Presence of Atypia or Disapperance of Atypia in RPFNA After 12 Months (for Both Arms) and 24 Months for Metformin Arm.
Measured: Up to 24 months
Compare Masood Cytology Score Value at 0 and 12 in Right and Left Breast From the Same Individual in the Metformin and Non-metformin Group.
Measured: Up to 24 months
Test the Reproducibility of RPPM in Duplicate RPPM Determinations From Individual RPFNA Specimens.
Measured: Up to 12 months
Correlate Baseline RPPM Values With Presence of Atypia at Month 12 and Month 24.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2013 (estimated)
- Study start23 Nov 2015
- Primary completion10 Nov 2023
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast Atypical Ductal HyperplasiaStudies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Victoria Seewaldt, MD, Study chair, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01905046
- Sponsor's protocol ID
- A211102
- Other IDs
- U10CA031946, NCI-2013-00995
- Status last verified
- Apr 2026
- First submitted
- 16 Jul 2013
- Last updated
- 8 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes